This White Rat has succeeded in persuading his GP to switch his hypertension medication to perindopril. Perindopril is an ACE inhibitor but is a little special. For one thing, it is one of only two that penetrate the BBB. For another it seems to increase dopamine levels and improve symptoms rather dramatically as the reports below indicate. I took the first one yesterday and another today and I do think that I see a change. I am going to experiment with time of day first. Assuming that my kidney function holds up (the only serious potential side effect) I will keep you all in the loop.

-------------------

1. Aust N Z J Med. 2000 Feb;30(1):48-53.

The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the
clinical features of Parkinson's disease.

Reardon KA, Mendelsohn FA, Chai SY, Horne MK.

Neurosciences Department, Monash Medical Centre, Melbourne, Vic.

BACKGROUND: Animal studies have demonstrated an interaction within the striatum
between the angiotensin and dopaminergic systems. In rats, the angiotensin
converting enzyme (ACE) inhibitor, perindopril, crosses the blood brain barrier
and increases striatal dopamine synthesis and release. In humans, angiotensin
type 1 receptors have been found on dopaminergic neurons in the substantia nigra
and striatum. In Parkinson's disease, there is a marked reduction of these
receptors associated with the nigrostriatal dopaminergic neuron loss.
AIMS: We performed a double blind placebo controlled crossover pilot study in
seven patients to investigate the effect of the ACE inhibitor, perindopril on the
clinical features of moderately severe Parkinson's disease.
RESULTS: After a four week treatment period with perindopril, patients had a
faster onset in their motor response to L-dopa and a reduction in 'on phase' peak
dyskinesia, p=0.021 and p=0.014 respectively. Patients also reported more 'on'
periods during their waking day in their movement diary, p=0.007. Perindopril was
well tolerated without any significant postural hypotension or renal dysfunction.
CONCLUSIONS: These results suggest that ACE inhibitors such as perindopril may
have a place in the management of motor fluctuations and dyskinesia in
Parkinson's disease and justify further study.


PMID: 10800878 [PubMed - indexed for MEDLINE]

For the first time today I caught myself thinking, "Damn! This stuff may actually be working!" I quickly stifled myself lest the Gods of Placebo be aroused but thought it time to report.

The first days were tough. Perindopril makes my symptoms worse for a couple of hours and I feel like crap, too. This is not a drug for taking when you need a boost. Things were not helped any by my GP's prescription of 8 mg daily when the manufacturer says start at 4 mg and go up to 8 mg after a month to get used to it. So I was a bit disappointed at first. But I twinked and fiddled and have found that 4 mg at bedtime avoids the problems.

I have fixed the problems that I created, but have I gained anything yet? Until today my answer would have had to have been, "Welllll, maybe." After all, it had barely been a week. While I had a feeling of favorable change, it was pretty vague and might have a certain amount of wishful thinking. And just last Friday, a mere three days ago, I had rushed home at mid-day just steps ahead of a couple of hours of "offtime". So I was a little paranoid and was going to be cautious.

Honestly, that was my intent. I don't know how I ended up at WallyWorld. Not just at it, but all over it for over an hour followed by a stop at a grocery store on the way home. Folks, I have pretty much been home bound for the last couple of weeks due to some problems with entacapone. Going up to the mail box in this heat had been a big deal. But today I surprised myself and conquered Mt. WalMart.

True, I did need an hour of recovery when I got home. But it beat collapsing in the floor with the pooches like I would have done a week ago. And tomorrow may be worse. But it may not. And it is true that I have a little dyskinesia. But I am trying to reproduce a bloomin' *40%* increase in the dopamine levels in my brain in one month's time! A little Dk is a sign that it may be happening, so I will start whittling the sinemet and requip down. Already have.

And so, onward - through the fog....

I joke around a bit, but perindopril is turning out to be a very serious matter. I am increasingly pleased with it. Things seem to be improving across the board. Off times have been limited to about an hour at mid-day and even that is dwindling. I no longer feel house bound and am out and about even with this blasted heat. It is an old drug, cheap, and well tested for hypertension. Any GP around can prescribe it if your neuro wont.

Gee Mr. White Rat,

I tend to joke around a bit too, but you continue to amaze me with your knowledge of whatever this Parkinsendocrine thing is that we suffer with. Good luck to you in your pursuit of answers Reverett un do trois.

sincerely jb49

Thank you jb49 and glad to see you here. The white rat thing is an old joke originally poking fun at our poverty (We can afford only one rat. Call me "squeaky" for short.)

Reverett123,

You amaze me with the knowledge you have of this disease. You sound like a doctor and really appreciate the way you keep us informed.

I just want to ask, so far has there been any side effects? If so, what have there been?

Please keep us informed as often as you can, I for one need the assurance that there's always some kind of hope for anyone caught in this dreadful disease.

thank you
keep up the good fight
cp

Other than the problems noted above that led me to bedtime as when to take it, I haven't noticed anything. Also the small study near the beginning of this thread doesn't mention any. My background is a little odd. I studied PD for three years alongside a French surgeon named Anne Frobert, herself a PWP.

Yesterday was the best in a very long time. No "off" time at all until nearly bedtime!

Like everything else about this dratted disease, nobody knows, so a guess will have to do. Angiotensin has strong pro-inflammatory action and the perindopril counters that. Since it is one of the few things able to pass the BBB, it is able to go deep into the brain and calm things down. That makes since to me but it is still a guess.

Yesterday (Sat 7/31) was another good day. No "off"time until evening when I cut short the medication day to see what would happen. Even that was improved. Most interestingly, I experienced a moment of, for lack of a better term, "fluidity" when my muscles worked smoothly as I turned my body. This is hard to explain, but it was as though my body realized that the turn was going to leave me open for a fall, belatedly began to brace for it, and was surprised when it did not materialize.

Another change- My medication cycle has an unfortunate feature. As sinemet comes on I must urinate. But this occurs before motor function returns. The result is that I make regular use of a chairside urinal. Or at least I did until yesterday when I realized that the whole day had passed with the urinal unused.

Found this review of the small study that started this thread:

"esults

Six subjects completed the study - one withdrew with nausea, malaise, and increasing 'off' periods while taking perindopril. After 4 weeks on the ACE inhibitor, 5 of the 6 had a significant increase in the area over the curve for their Webster scores, indicating an increased motor response to their standardized dose of L-dopa. There was a faster onset, and a reduction in 'on' phase peak dyskinesia.

The UPDRS II scores showed that perindopril was associated with improved functional ability in 'off' phases. The patient diaries revealed a modest but significant increase in 'on' periods during ACE inhibitor treatment, which was maximal in the 3rd and 4th weeks on the drug.

While peak dyskinesia scores were reduced, four of six patients had an increase in dyskinesia during the waking day with perindopril. This was probably a reflection of their increased total 'on' times.

There were no perindopril-related adverse effects on blood pressure, postural hypotension, or renal function.

Comment

This study confirmed the concept that an ACE inhibitor can improve the motor response to L-dopa in patients with Parkinson's disease. The drug also increased the proportion of the day spent in the 'on' state, as well as showing an improvement in the functional disability scale used.

Most effective agents in Parkinson's disease induce dyskinesia; perindopril, on the other hand, produced a greater amplitude of motor response to L-dopa with a reduction in peak dyskinesia, i.e. it seems to have an effect beyond simply increasing dopamine release.

The authors of the study point out that the benefits of perindopril were "modest, and not of the magnitude of L-dopa itself". However, the dose was relatively small, and treatment duration was short. As tolerance as good, there is every reason to conduct further studies with higher doses, for longer treatment periods.

Trandolopril, spiropril and perindopril are ACE inhibitors that can penetrate the blood-brain barrier, while enalapril cannot."

Patents are mind-numbing, but if anyone wants to interpret for the rest of us

Neurogenesis by modulating angiotensin
United States Patent 7858611